As an extension to our current studies on new anti-HIV tannins and their analogs as well as other related natural products, the long-term objective of this research is to discover novel useful anti-HIV compounds from plant-derived natural products and their analogs. Specifically, we propose continuously to isolate and characterize the potent anti-HIV principles from extracts of 33 plant species which have never been investigated previously for their anti-HIV constituents. These extracts have already demonstrated potent inhibitory effects on HIV replication in H9 lymphocyte cells and HIV reverse transcriptase. Extraction, fractionation, and isolation of the active principles will be guided at every stage by an in vitro P24 antigen capture assay in H9 lymphocyte cells. Following the above bioassay-directed isolation of the active principles, the determination of their structures will be carried out by modern physical methods, including spectral and X-ray analyses. Mechanism of action studies will be conducted in cell culture-based assays. Structural modification and synthesis of analogs of selected new active leads in order to elucidate their structure-activity relationships, as well as to improve their pharmacological profiles will also be initiated.